Author/Editor		Kristan, Katja; Sova, Matej; Lunder, Mojca; Bratkovič, Tomaž; Gobec, Stanislav; Štrukelj, Borut; Stojan, Jure; Adamski, Jerzy; Lanišnik-Rižner, Tea
Title		Searching for inhibitors of fungal 17beta-hydroxysteroid dehydrogenase
Type		članek
Source		In: Weiner H, Maser E, Lindahl R, et al, editors. Enzymology and molecular biology of carbonyl metabolism. Vol 13. Purdue: Purdue University,
Publication year		2007
Volume		str. 263-72
Language		eng
Abstract		17beta-Hydroxysteroid dehydrogenases (17(beta-HSDs) have key roles in hormonal regulation and function in the human, and as such they represent emerging therapeutic targets for the control of estrogen- and androgen-dependent diseases. Our model enzyme is 17beta-HSD from the fungus Cochliobolus lunatus 17(beta-HSDcI), and we have used different approaches to find potent inhibitors of this enzyme. Using "classical" inhibition assays, we have shown that some phytoestrogens and cinnamic acid esters are potent in their inhibition of the oxidation of 4-estrene-17beta-o1-3-one and the reduction of 4estrene-3,17-dione catalyzed by 17beta-HSDcI. We have also examined peptides as potential inhibitors of 17beta-HSDcI on the basis that this enzyme is a homodimer under native conditions. Thus, compounds that specifically prevent the formation of dimers could represent a new class of inhibitors, since dimerization is a prerequisite for catalysis. We have shown that a 33-amino-acid-long peptide binds to the dimerization surface, prevents the formation of dimers, and consequently inhibits 17betaHSDcI. Finally, we also show that phage display provides another tool in the search for inhibitors that bind to the surface or in the active site of 17betaH SDcI.
Descriptors		17-HYDROXYSTEROID DEHYDROGENASES ENZYME INHIBITORS ASCOMYCETES ESTROGENS